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translator: joseph genireviewer: morton bast i'll never forget that day back in the spring of 2006. i was a surgical resident at the johns hopkins hospital, taking emergency call. i got paged by the e.r. around 2 in the morning to come and see a woman with a diabetic ulcer on her foot.
i can still remember sort of that smell of rotting flesh as i pulled the curtain back to see her. and everybody there agreed this woman was very sick and she needed to be in the hospital. that wasn't being asked. the question that was being asked of me was a different one, which was, did she also need an amputation? now, looking back on that night, i'd love so desperately to believe that i treated that woman
on that night with the same empathy and compassion i'd shown the 27-year-old newlywed who came to the e.r. three nights earlier with lower back pain that turned out to be advanced pancreatic cancer. in her case, i knew there was nothing i could do that was actually going to save her life. the cancer was too advanced. but i was committed to making sure that
i could do anything possible to make her stay more comfortable. i brought her a warm blanket and a cup of a coffee. i brought some for her parents. but more importantly, see, i passed no judgment on her, because obviously she had done nothing to bring this on herself. so why was it that, just a few nights later, as i stood in that same e.r. and determined
that my diabetic patient did indeed need an amputation, why did i hold her in such bitter contempt? you see, unlike the woman the night before, this woman had type 2 diabetes. she was fat. and we all know that's from eating too much and not exercising enough, right? i mean, how hard can it be? as i looked down at her in the bed, i thought to myself,
if you just tried caring even a little bit, you wouldn't be in this situation at this moment with some doctor you've never met about to amputate your foot. why did i feel justified in judging her? i'd like to say i don't know. but i actually do. you see, in the hubris of my youth, i thought i had her all figured out.
she ate too much. she got unlucky. she got diabetes. case closed. ironically, at that time in my life, i was also doing cancer research, immune-based therapies for melanoma, to be specific, and in that world i was actually taught to question everything, to challenge all assumptions and hold them to the highest possible scientific standards. yet when it came to a disease like diabetes
that kills americans eight times more frequently than melanoma, i never once questioned the conventional wisdom. i actually just assumed the pathologic sequence of events was settled science. three years later, i found out how wrong i was. but this time, i was the patient. despite exercising three or four hours every single day, and following the food pyramid to the letter, i'd gained a lot of weight and developed something
called metabolic syndrome. some of you may have heard of this. i had become insulin-resistant. you can think of insulin as this master hormone that controls what our body does with the foods we eat, whether we burn it or store it. this is called fuel partitioning in the lingo. now failure to produce enough insulin is incompatible with life. and insulin resistance, as its name suggests,
is when your cells get increasingly resistant to the effect of insulin trying to do its job. once you're insulin-resistant, you're on your way to getting diabetes, which is what happens when your pancreas can't keep up with the resistance and make enough insulin. now your blood sugar levels start to rise, and an entire cascade of pathologic events sort of spirals out of control that can lead to heart disease,
cancer, even alzheimer's disease, and amputations, just like that woman a few years earlier. with that scare, i got busy changing my diet radically, adding and subtracting things most of you would find almost assuredly shocking. i did this and lost 40 pounds, weirdly while exercising less. i, as you can see, i guess i'm not overweight anymore. more importantly, i don't have insulin resistance. but most important, i was left
with these three burning questions that wouldn't go away: how did this happen to me if i was supposedly doing everything right? if the conventional wisdom about nutrition had failed me, was it possible it was failing someone else? and underlying these questions, i became almost maniacally obsessed in trying to understand the real relationship between obesity and insulin resistance.
now, most researchers believe obesity is the cause of insulin resistance. logically, then, if you want to treat insulin resistance, you get people to lose weight, right? you treat the obesity. but what if we have it backwards? what if obesity isn't the cause of insulin resistance at all? in fact, what if it's a symptom of a much deeper problem, the tip of a proverbial iceberg?
i know it sounds crazy because we're obviously in the midst of an obesity epidemic, but hear me out. what if obesity is a coping mechanism for a far more sinister problem going on underneath the cell? i'm not suggesting that obesity is benign, but what i am suggesting is it may be the lesser of two metabolic evils. you can think of insulin resistance as the reduced capacity
of our cells to partition fuel, as i alluded to a moment ago, taking those calories that we take in and burning some appropriately and storing some appropriately. when we become insulin-resistant, the homeostasis in that balance deviates from this state. so now, when insulin says to a cell, i want you to burn more energy than the cell considers safe, the cell, in effect, says,
"no thanks, i'd actually rather store this energy." and because fat cells are actually missing most of the complex cellular machinery found in other cells, it's probably the safest place to store it. so for many of us, about 75 million americans, the appropriate response to insulin resistance may actually be to store it as fat, not the reverse, getting insulin resistance in response to getting fat. this is a really subtle distinction,
but the implication could be profound. consider the following analogy: think of the bruise you get on your shin when you inadvertently bang your leg into the coffee table. sure, the bruise hurts like hell, and you almost certainly don't like the discolored look, but we all know the bruise per se is not the problem. in fact, it's the opposite. it's a healthy response to the trauma, all of those immune cells rushing to the site of the injury
to salvage cellular debris and prevent the spread of infection to elsewhere in the body. now, imagine we thought bruises were the problem, and we evolved a giant medical establishment and a culture around treating bruises: masking creams, painkillers, you name it, all the while ignoring the fact that people are still banging their shins into coffee tables. how much better would we be if we treated the cause --
telling people to pay attention when they walk through the living room -- rather than the effect? getting the cause and the effect right makes all the difference in the world. getting it wrong, and the pharmaceutical industry can still do very well for its shareholders but nothing improves for the people with bruised shins. cause and effect.
so what i'm suggesting is maybe we have the cause and effect wrong on obesity and insulin resistance. maybe we should be asking ourselves, is it possible that insulin resistance causes weight gain and the diseases associated with obesity, at least in most people? what if being obese is just a metabolic response to something much more threatening,
an underlying epidemic, the one we ought to be worried about? let's look at some suggestive facts. we know that 30 million obese americans in the united states don't have insulin resistance. and by the way, they don't appear to be at any greater risk of disease than lean people. conversely, we know that six million lean people in the united states are insulin-resistant,
and by the way, they appear to be at even greater risk for those metabolic diseases i mentioned a moment ago than their obese counterparts. now i don't know why, but it might be because, in their case, their cells haven't actually figured out the right thing to do with that excess energy. so if you can be obese and not have insulin resistance, and you can be lean and have it, this suggests that obesity may just be a proxy
for what's going on. so what if we're fighting the wrong war, fighting obesity rather than insulin resistance? even worse, what if blaming the obese means we're blaming the victims? what if some of our fundamental ideas about obesity are just wrong? personally, i can't afford the luxury of arrogance anymore, let alone the luxury of certainty.
i have my own ideas about what could be at the heart of this, but i'm wide open to others. now, my hypothesis, because everybody always asks me, is this. if you ask yourself, what's a cell trying to protect itself from when it becomes insulin resistant, the answer probably isn't too much food. it's more likely too much glucose: blood sugar. now, we know that refined grains and starches
elevate your blood sugar in the short run, and there's even reason to believe that sugar may lead to insulin resistance directly. so if you put these physiological processes to work, i'd hypothesize that it might be our increased intake of refined grains, sugars and starches that's driving this epidemic of obesity and diabetes, but through insulin resistance, you see, and not necessarily through just overeating and under-exercising.
when i lost my 40 pounds a few years ago, i did it simply by restricting those things, which admittedly suggests i have a bias based on my personal experience. but that doesn't mean my bias is wrong, and most important, all of this can be tested scientifically. but step one is accepting the possibility that our current beliefs about obesity, diabetes and insulin resistance could be wrong
and therefore must be tested. i'm betting my career on this. today, i devote all of my time to working on this problem, and i'll go wherever the science takes me. i've decided that what i can't and won't do anymore is pretend i have the answers when i don't. i've been humbled enough by all i don't know. for the past year, i've been fortunate enough to work on this problem with the most amazing team
of diabetes and obesity researchers in the country, and the best part is, just like abraham lincoln surrounded himself with a team of rivals, we've done the same thing. we've recruited a team of scientific rivals, the best and brightest who all have different hypotheses for what's at the heart of this epidemic. some think it's too many calories consumed. others think it's too much dietary fat.
others think it's too many refined grains and starches. but this team of multi-disciplinary, highly skeptical and exceedingly talented researchers do agree on two things. first, this problem is just simply too important to continue ignoring because we think we know the answer. and two, if we're willing to be wrong, if we're willing to challenge the conventional wisdom with the best experiments science can offer,
we can solve this problem. i know it's tempting to want an answer right now, some form of action or policy, some dietary prescription -- eat this, not that â€” but if we want to get it right, we're going to have to do much more rigorous science before we can write that prescription. briefly, to address this, our research program is focused around three meta-themes, or questions.
first, how do the various foods we consume impact our metabolism, hormones and enzymes, and through what nuanced molecular mechanisms? second, based on these insights, can people make the necessary changes in their diets in a way that's safe and practical to implement? and finally, once we identify what safe and practical changes people can make to their diet, how can we move their behavior in that direction
so that it becomes more the default rather than the exception? just because you know what to do doesn't mean you're always going to do it. sometimes we have to put cues around people to make it easier, and believe it or not, that can be studied scientifically. i don't know how this journey is going to end, but this much seems clear to me, at least:
we can't keep blaming our overweight and diabetic patients like i did. most of them actually want to do the right thing, but they have to know what that is, and it's got to work. i dream of a day when our patients can shed their excess pounds and cure themselves of insulin resistance, because as medical professionals,
we've shed our excess mental baggage and cured ourselves of new idea resistance sufficiently to go back to our original ideals: open minds, the courage to throw out yesterday's ideas when they don't appear to be working, and the understanding that scientific truth isn't final, but constantly evolving. staying true to that path will be better for our patients and better for science.
if obesity is nothing more than a proxy for metabolic illness, what good does it do us to punish those with the proxy? sometimes i think back to that night in the e.r. seven years ago. i wish i could speak with that woman again. i'd like to tell her how sorry i am. i'd say, as a doctor, i delivered the best clinical care i could,
but as a human being, i let you down. you didn't need my judgment and my contempt. you needed my empathy and compassion, and above all else, you needed a doctor who was willing to consider maybe you didn't let the system down. maybe the system, of which i was a part, was letting you down.
if you're watching this now, i hope you can forgive me. (applause)